Isotope-effects in reactions

Brown and McDonald (1966) provided another type of kinetic evidence for these size relationships by determining secondary kinetic isotope effects in reactions of pyridine-4-pyridines with alkyl iodides. For example, the isotopic rate ratio in the reaction between 4-(methyl-d3)-pyridine and methyl iodide at 25-0 C in nitrobenzene solution was determined to be kjyfk = l-OOl, while that in the corresponding reaction with 2,6-(dimethyl-d6)-pyridine was 1-095. (Brown and McDonald (1966) estimate an uncertainty of 1% in the k jk values.) Furthermore, the isotopic rate ratio in the case of the 2-(methyl-d3)-compound increased from 1 030 to 1-073 as the alkyl group in the alkyl iodide was changed from methyl to isopropyl, i.e. the isotope effect increased with increasing steric requirements of the alkyl iodide. 

Concerning the change in or for isotopic substitution, cnrrently there is not much data and the exact pattern of the phenomenon is still not known. Nevertheless, it seems useful to compare the existing data both for the consideration of isotopic effects in reactions and for information on the possible new ways of nsing electron transfer for a more effective enrichment of isotopic mixtnres with one specihc isotope form. 

It is known that the isotope effect may occur not only because of tunneling. Within the framework of the transition-state theory, which does not take tunneling into account, the isotope effect is explained by the variations of the energies of the ground vibrational levels and by the variations of the partition functions of the reagents and of the activated complex upon changing one isotope for another [53]. To make it clear to what extent the isotope effect in reactions (a) (d) is connected with tunneling, it is useful to mention... 

Substitution of deuterium at the )3 position leads to the /3 deuterium isotope effect in reactions like 2.79. 

The isotope effect in reactions of hydrogen, however, can also be put to work to give us information as to the details of certain reactions (that is, establishing possible reaction mechanisms) (Exercise 10). 

These results show an isotope effect in reaction (2) which has also been observed at low temperatures. By combining ki with the equilibrium constant K for Brj dissociation, a value of 8.3+0.7 was obtained for the rate coefficient ratio k fk. This compares very favorably with the value 8.4+0.6 obtained at lower tempera-... 

Deuterium substitution may give rise to important effects on the reaction kinetics. The maximum kinetic isotope effect is obtained when the bond is broken in the transition state (primary isotope effect). In reactions involving several stages, isotope effects can naturally be observed only if the bond to the isotope is broken in the rate-determining step . In this case, deuterium substitution would be expected to depress the reaction rate. We give below two examples relative to acetylenes, showing how the effect, kulkn, may specify the reaction process or, on the contrary, allow the rejection of a possible mechanism. 

The secondary -deuterium kinetic isotope effects in reactions of -perdeuterated ethyl-, isopropyl- and rm-butylmagnesium halides with four different ketones were described [24] and were found to be small (within 5%). There, too, hyperconjugative stabilization was supposed to play a role, but this effect was opposed by the steric effects. The role of hyperconjugation in reactions of Grignard reagents, therefore, seems complicated and requires further studies. 

L. Melander, W. H. Saunders, Jr. Reaction Rates of Isotopic Molecules, Wiley, New York, 1980, Ch. 10 Isotope Effects in Reactions with Complex Mechanisms. 

The intermolecular isotope effect in reactions 110 and 111 for 2.8eV tritium atoms generated by photolysis of TBr at 1849 A, as measured by the ratio [(CH3T/CH4)/(CD3T/CD4)], has been found to equal 7.2. The ratio for the intramolecular competition for the T for H versus T for D substitution in partially deuteriated methanes (equations 112 and 113) is approximately unity, as measured semi-quantitatively by the ratio of product yields, [CHD2T]/[CH2DT] = 1.06 + 0.1. 

Isotope effects on reaction rates have been studied intensively, and will receive the major share of the space in this chapter. This field has been reviewed on a number of previous occasions (Me-lander, 1960 Saunders, 1961 Bigeleisen and Wolfsberg, 1959). The present chapter is not intended to be comprehensive or rigorous its aim is to present qualitatively the theory of isotope effects, and to demonstrate with appropriate examples the use of isotope effects in reaction mechanisms studies. 

Because of the cancellations described in the preceding paragraphs, it is often possible to obtain close approximations to the true isotope effects in reactions of polyatomic molecules using models for calculation that are much simpler than the molecules themselves. Even the diatomic model, A—B, with which we began our discussion, is frequently successful. For some reactions, however, it can be seriously misleading. This is especially true in the treatment of proton transfers, where it does not consider the base (or solvent molecule) that must be present to remove the proton (Westheimer, 1961). 

Another consequence of Fig. 3 (and of the harmonic oscillator approximation as well) is that the H—X vibration will have a slightly greater maximum amplitude than the D—X vibration. The space required by the hydrogen atom will thus be somewhat greater than that occupied by the deuterium atom. One could then imagine a steric secondary isotope effect in reactions which either increased or decreased crowding of isotopically substituted hydrogens. 

Small kinetic isotope effects in reactions of 3-deuteriated Grignard reagents, e.g. with PhCOPh or MeCOCgHj3, have been determinedly by isoh ic sqtaiadon of reacticm products by capillary GC. 

Muckerman JT (1971) Monte carlo calculations of energy partitioning and isotope effects in reactions of fluorine atoms with H2, HD, and D2. J Chem Phys 54(3) 1155... 

A study by Dolbier and Dai of secondary deuterium isotope effects in reactions of deuteriated allenes with various olefins and dienes led to the conclusion that all [2 + 2] four-electron thermal cycloadditions, including dimerization, are multistep processes, whereas [2 -I- 3] and [2 + 4] six-electron thermal cycloadditions are concerted. Thus allenes are demoted to the rank of relatively reactive alkenes. ... 

A further method for obtaining Bronsted exponents is to compare kinetic and equilibrium acidities for proton transfers from the isotopic bases HjO and D2O [5, 76, 77]. This involves measurement of the secondary isotope effects in reactions of the type... 

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